Blood glucose to predict symptomatic intracranial hemorrhage after endovascular treatment of acute ischemic stroke with large infarct core: a prospective observational study.

Introduction: Symptomatic intracranial hemorrhage (sICH) is a serious complication of acute ischemic stroke (AIS) after endovascular treatment (EVT). Limited data exist regarding predictors and clinical implications of sICH after EVT, underscoring the significance of identifying risk factors to enhance prevention strategies. Therefore, the main objective of this study was to evaluate the incidence of sICH and identify its predictors after EVT in patients with large infarct core-AIS in the pre-circulation stage. Methods: Using data from the EVT for the Pre-circulation Large Infarct Core-AIS Study, we enrolled patients who were treated with EVT from the Prospective Multicenter Cohort Study of Early Treatment in Acute Stroke (MAGIC) registry. Baseline demographics, medical history, vascular risk factors, blood pressure, stroke severity, radiographic features, and EVT details were collected. The patients were classified into three groups: without intracranial hemorrhage (ICH), with asymptomatic intracranial hemorrhage (aICH), and sICH, based upon the occurrence of sICH. The main outcomes were the occurrence of sICH according to the Heidelberg Bleeding Classification and functional condition at 90 days. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to identify independent predictors of sICH after EVT. Results: The study recruited a total of 490 patients, of whom 13.3% (n = 65) developed sICH. Patients with sICH had less favorable outcomes than those without intracranial hemorrhage (ICH) and those with aICH (13.8% vs. 43.5% vs. 32.2%, respectively; p < 0.001). The overall mortality was 41.8% (n = 205) at 90 days post-EVT. The univariate analysis revealed significant differences among the three groups in terms of blood glucose levels at admission, probability of favorable outcomes, incidence of brain herniation, and 90-day mortality. The multifactorial logistic regression analysis revealed that the blood glucose level at admission [odds ratio (OR) 1.169, p < 0.001, confidence interval (CI) 1.076-1.269] was an independent predictor of sICH. A blood glucose level of 6.95 mmol/L at admission was the best predictor of sICH, with an area under the ROC curve (AUC) of 0.685 (95% CI: 0.616-0.754). Discussion: The study findings demonstrated that the probability of sICH after EVT was 13.3% in patients with pre-circulation large infarct core-AIS, and sICH increased the risk of an unfavorable prognosis. Higher blood glucose levels at admission were associated with sICH after EVT in patients with pre-circulation large infarct core AIS. These findings underscore the importance of early management strategies to mitigate this risk.

Endovascular Therapy and Outcomes Among Patients With Very Large Ischemic Core Stroke.

Importance: The association of endovascular therapy (EVT) with outcomes is unclear for patients with very low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) within 24 hours of stroke onset. Objective: To explore the association of EVT with functional and safety outcomes among patients with ASPECTS of 0 to 2 scored with noncontrast computed tomography. Design, Setting, and Participants: This cohort study used data from an ongoing, prospective, observational, nationwide registry including all patients treated at 38 stroke centers in China with an occlusion in the internal carotid artery or M1 or M2 segment of the middle cerebral artery within 24 hours of witnessed symptom onset. Patients with ASPECTS of 0 to 2 between November 1, 2021, and February 8, 2023, were included in analysis. Data were analyzed October to November 2023. Exposures: EVT vs standard medical treatment (SMT). Main Outcomes and Measures: The primary outcome was favorable functional outcome, defined as modified Rankin Scale score (mRS) of 0 to 3, at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 48 hours and mortality at 90 days. Results: A total of 245 patients (median [IQR] age, 71 [63-78] years; 118 [48%] women) with ASPECTS of 0 to 2 were included, of whom 111 patients (45.1%) received SMT and 135 patients (54.9%) received EVT. The EVT group had significantly greater odds of favorable functional outcome at 90 days than the SMT group (30 patients [22.2%] vs 11 patients [9.9%]; P = .01; adjusted odds ratio [aOR], 3.07 [95% CI, 1.29-7.31]; P = .01). Patients in the EVT group, compared with the SMT group, had significantly greater odds of any ICH (56 patients [41.5%] vs 16 patients [11.4%]; P < .001; aOR, 4.27 [95% CI, 2.19-8.35]; P < .001) and sICH (24 patients [17.8%] vs 1 patient [0.9%]; P < .001; aOR, 23.07 [95% CI, 2.99-177.79]; P = .003) within 48 hours. There were no differences between groups for 90-day mortality (80 patients [59.3%] vs 59 patients [53.2%]; P = .34; aOR, 1.38 [95% CI, 0.77-2.47]; P = .28). The results remained robust in the propensity score-matched analysis. Conclusions and Relevance: In this cohort study of patients with very low ASPECTS based on NCCT within 24 hours of stroke onset, those treated with EVT had higher odds of a favorable functional outcome compared with those who received SMT. Randomized clinical trials are needed to assess these findings.

Endovascular treatment versus standard medical treatment in patients with established large infarct: a cohort study.

BACKGROUND: Previous trials confirmed the benefit of endovascular treatment (EVT) in acute large core stroke, but the effect of EVT on outcomes in these patients based on non-contrast computed tomography (NCCT) in real-world clinical practice was unclear. The aim of this study was to explore the effect of EVT versus standard medical treatment (SMT) in patients with large ischemic core stroke defined as Alberta Stroke Program Early CT Score (ASPECTS)≤5 based on NCCT alone. MATERIALS AND METHODS: Patients with acute large core stroke at 38 Chinese centers between November 2021 and February 2023 were reviewed from prospectively maintained databases. The primary outcome was favorable functional outcome (modified Rankin Scale score [mRS], 0-3) at 90 days. Safety outcomes included 48-hour symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. RESULTS: Of 745 eligible patients recruited at 38 stroke centers between November 2021 and February 2023, 490 were treated with EVT and 255 with SMT alone. One hundred and eighty-one (36.9%) in the EVT group achieved favorable functional independence versus 48 (18.8%) treated with SMT only (adjusted risk ratio [RR], 1.86; 95% CI, 1.43 to 2.42, P<0.001; adjusted risk difference [RD], 13.77; 95% CI, 7.40 to 20.15, P<0.001). The proportion of sICH was significantly higher in patients undergoing EVT (13.3% vs. 2.4%; adjusted RR, 5.17; 95% CI, 2.17 to 12.32, P<0.001; adjusted RD, 10.10; 95% CI, 6.12 to 14.09, P<0.001). No significant difference of mortality between the groups was observed (41.8% vs. 49.0%; adjusted RR, 0.91; 95% CI, 0.77 to 1.07, P=0.24; adjusted RD, -5.91; 95% CI, -12.91 to 1.09, P=0.1). CONCLUSION: Among patients with acute large core stroke based on NCCT in real world, EVT is associated with better functional outcomes at 90 days despite of higher risk of sICH. Rates of procedure-related complications were high in the EVT group.

Short-Term Effect of Ambient Temperature in Acute Ischemic Stroke with Endovascular Treatment Due to Large Vessel Occlusion.

Purpose: Acute ischemic stroke (AIS) stands as the primary cause of mortality and extended disability globally. While prior studies have examined the connection between stroke and local weather, they have produced conflicting results. Our goal was to examine the correlation between temperature and functional prognosis in patients with large vessel occlusion (LVO) undergoing endovascular therapy (EVT). Patients and methods: This study included a total of 1809 patients. Temperatures from stroke onset to groin puncture were categorized into Cold (10th percentile of temperature), Cool (10th-50th percentile of temperature), Warm (50th-90th percentile of temperature), and Hot (90th percentile of temperature) groups. The primary efficacy result was the modified Rankin Scale (mRS) score at 90 days. Safety outcomes included mortality, symptomatic intracranial hemorrhage (sICH) and complications after cerebral infarction. Results: The primary efficacy results demonstrated a statistical enhancement in functional outcomes at 90 days for patients in the Warm group compared to the Cold group (adjusted common odds ratio [OR]: 1.386; 95% confidence interval [CI]: 1.024-1.878, P=0.035). Secondary efficacy results showed that temperature was associated with a higher rate of 90-day functional independence (adjusted OR: 1.016; 95% CI: 1.004-1.029; P=0.009), which was higher in the Warm group compared with patients in the Cold group (adjusted OR: 1.646; 95% CI: 1.107-2.448, P=0.014). There were no significant differences between groups in terms of sICH, 90-day mortality, and post-infarction complications. Conclusion: Compared with Cold temperature, Warm temperature is associated with better functional outcomes and reduced mortality risk without increasing the risk of sICH.

The effectiveness and safety of human urinary kallidinogenase in acute ischemic stroke patients undergoing endovascular therapy.

The effectiveness and safety of human urinary kallidinogenase (HUK) in acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT) due to large vessel occlusion (LVO) was unclear. A pooled analysis was performed using individual data from the DEVT and RESCUE BT trials. Patients were divided into two groups based on HUK treatment. The primary outcome was the 90-day modified Rankin Scale (mRS) score. Safety outcomes included 90-day mortality and symptomatic intracranial hemorrhage (sICH) within 48 hours. A total of 1174 patients were included in the study. Of these, 150 (12.8%) patients received HUK. The adjusted common odds ratio (OR) of the mRS score was 1.458 (95% confidence interval [CI] = 1.072-1.983; p = 0.016) favoring HUK. The incidence of sICH (2.0% vs. 8.6%; adjusted OR: 0.198; 95% CI: 0.061-0.638; p = 0.007) and mortality (11.3% vs.18.5%; adjusted OR: 0.496; 95% CI: 0.286-0.862; p = 0.013) was lower in HUK group than non-HUK group. This association was consistent with propensity score-matching and the inverse probability of treatment weighting analysis. In conclusion, HUK was safe and associated with a preferable prognosis in AIS patients due to LVO in the anterior circulation.

The Association Between National Institutes of Health Stroke Scale Score and Clinical Outcome in Patients with Large Core Infarctions Undergoing Endovascular Treatment.

INTRODUCTION: This study aimed to analyze the association between baseline National Institutes of Health Stroke Scale (NIHSS) scores and clinical outcomes in patients with large core infarctions undergoing endovascular treatment (EVT), a relationship that remains unclear. METHODS: Data were obtained from the MAGIC study, a prospective multicenter cohort study focusing on patients with acute large core ischemic stroke. This analysis evaluated the impact of NIHSS scores on EVT outcomes in patients with large core infarctions. Primary outcome metrics included favorable outcomes (modified Rankin Scale [mRS] of 0-3 at 90 days), while secondary outcomes encompassed shifts in mRS scores, functional independence (mRS score of 0-2), mRS score of 0-4, and successful recanalization rates. Adverse events considered were symptomatic intracranial hemorrhage (sICH) and mortality. RESULTS: A total of 490 patients were enrolled in this study. Higher baseline NIHSS scores were inversely correlated with favorable outcomes (adjusted odds ratio [OR] in model 3, 0.848 [0.797-0.903], P < 0.001), particularly in patients with NIHSS scores above 20 (adjusted OR in model 3, 0.518 [0.306-0.878] vs. 0.290 [0.161-0.523]). Regarding adverse events, higher baseline NIHSS scores significantly correlated with increased 90-day mortality rates (adjusted OR in model 3, 1.129 [1.072-1.189], P < 0.001). This correlation became insignificant when baseline NIHSS scores exceeded 22. Additionally, baseline NIHSS scores partially mediated the association between age (indirect effect = - 0.0005, 19.39% mediated) and sex (indirect effect = 0.0457, 25.08% mediated) with the primary outcome. CONCLUSIONS: The findings indicate that higher baseline NIHSS scores correlate with poorer outcomes and increased mortality, particularly when scores exceed 20. Moreover, age and sex indirectly influence favorable outcomes through their association with baseline NIHSS scores.

Time to Treatment With Intravenous Thrombolysis Before Thrombectomy and Functional Outcomes in Acute Ischemic Stroke: A Meta-Analysis.

Importance: The benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy. Objective: To determine whether the benefit associated with IVT plus thrombectomy vs thrombectomy alone decreases with treatment time from symptom onset. Design, Setting, and Participants: Individual participant data meta-analysis from 6 randomized clinical trials comparing IVT plus thrombectomy vs thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2313). Exposure: Interval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy vs thrombectomy alone. Main Outcomes and Measures: The primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT. Results: In 2313 participants (1160 in IVT plus thrombectomy group vs 1153 in thrombectomy alone group; median age, 71 [IQR, 62 to 78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common odds ratio [OR] per 1-hour delay, 0.84 [95% CI, 0.72 to 0.97], P = .02 for interaction). The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13 to 1.96] at 1 hour, 1.25 [95% CI, 1.04 to 1.49] at 2 hours, and 1.04 [95% CI, 0.88 to 1.23] at 3 hours). For a mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3% to 16%) at 1 hour, 5% (95% CI, 1% to 9%) at 2 hours, and 1% (95% CI, -3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes. Conclusions and Relevance: In patients presenting at thrombectomy-capable stroke centers, the benefit associated with IVT plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of IVT was short.

The impact of stress hyperglycemia ratio on short-term and long-term outcomes for acute basilar artery occlusion underwent endovascular treatment.

BACKGROUND: Stress hyperglycemia ratio (SHR) reflects a true acute hyperglycemic state during acute basilar artery occlusion (ABAO). We aimed to investigate the association between SHR and short-term and long-term outcomes in patients with ABAO receiving endovascular treatment (EVT). METHODS: We selected patients treated with EVT from the BASILAR study, a nationwide prospective registry. A total 250 patients with documented glucose and glycated hemoglobin (HbA1C) values at admission were included. SHR was calculated as the ratio of glucose/HbA1C. All 250 patients completed 90 days of follow-up and 234 patients (93.6%) completed 1 year of follow-up. The primary outcome was the favorable outcome defined as modified Rankin Scale (mRS) score ≤ 3 at 90 days. Safety outcomes included mortality at 90 days and 1 year, and intracranial hemorrhage. RESULTS: Among the 250 patients included, patients with higher tertiles of SHR were associated with decreased odds of a favorable functional outcome at 90 days (adjusted OR, 0.26; 95% CI, 0.12-0.56; P = 0.001 and adjusted OR, 0.37; 95% CI, 0.18-0.80; P = 0.01; respectively) and 1 year (adjusted OR, 0.34; 95% CI, 0.16-0.73; P = 0.006 and adjusted OR, 0.38; 95% CI, 0.18-0.82; P = 0.01; respectively) after adjusting for confounding covariates. The mortality was comparable across tertiles of SHR groups at 90 days and 1 year. CONCLUSIONS: Our study showed that SHR was associated with a decreased probability of favorable functional outcome both at 90 days and 1 year after EVT in patients with ABAO. The relationship was more pronounced in non-diabetes patients. TRIAL REGISTRATION: Clinical Trial Registry Identifier: ChiCTR1800014759 (November 12, 2013).

Endovascular Therapy for Basilar Artery Occlusion in Sudden Onset to Maximal Deficit Ischemic Events.

BACKGROUND: The presence of sudden onset to maximal deficit (SOTMD) in patients with acute basilar artery occlusion often results in more severe outcomes. However, the effect of endovascular therapy on SOTMD and whether the outcome is affected by onset-to-puncture time remain unclear. METHODS AND RESULTS: This retrospective analysis was conducted using data from the prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry). Consecutive patients with basilar artery occlusion receiving endovascular therapy were dichotomized into SOTMD and non-SOTMD cohorts. The primary outcomes included a favorable outcome (modified Rankin scale 0-3), recanalization, and mortality at 90 days. The outcomes of patients with SOTMD were analyzed using multivariable logistic regression. In the multivariate analysis, a favorable outcome was similar between the two cohorts (odds ratio [OR], 0.88 [95% CI, 0.58-1.34]; P=0.5), although the mortality of patients with SOTMD was higher than that of patients with non-SOTMD (OR, 1.67 [95% CI, 1.14-2.44]; P=0.008). The probability of mortality increased from 40.0% at 1 hour to 70.0% at 6 hours in the SOTMD cohort, and favorable outcomes of patients with non-SOTMD declined from 38.0% at 1 hour to 18.0% at 8 hours. CONCLUSIONS: No significant difference was observed in favorable outcomes between the SOTMD and non-SOTMD groups, although mortality was higher in the SOTMD cohort. The patients with SOTMD had a stronger time dependence for endovascular therapy in terms of mortality, while the time dependency regarding favorable outcome in the NSOTMD group was even higher. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800014759.

Systemic THrombolysis Randomization IN Endovascular Stroke Therapy (SHRINE) Collaboration: a patient-level pooled analysis of the SKIP and DEVT Trials.

OBJECTIVE: To evaluate the non-inferiority of endovascular treatment (EVT) alone versus intravenous thrombolysis (IVT) followed by EVT and to assess its heterogeneity across prespecified subgroups. METHODS: We pooled data from two trials (SKIP in Japan; DEVT in China). Individual patient data were pooled to assess outcomes and heterogeneity of treatment effect. The primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: We included 438 patients (217 EVT alone; 221 combined IVT+EVT). The meta-analysis failed to demonstrate the non-inferiority of EVT alone over combined IVT+EVT in achieving 90-day functional independence (56.7% vs 51.6%; adjusted common odds ratio (cOR)=1.27, 95% CI 0.84 to 1.92, pnon-inferiority=0.06). Effect sizes favoring EVT alone were present with stroke onset to puncture time longer than 180 min (cOR=2.28, 95% CI 1.18 to 4.38, pinteraction ≤180 vs >180 min=0.02) and intracranial internal carotid artery ICA occlusions (for ICA cOR=3.04, 95% CI 1.10 to 8.43, pinteraction ICA vs MCA=0.08). The rates of sICH (6.5% vs 9.0%; cOR=0.77, 95% CI 0.37 to 1.61) and 90-day mortality (12.9% vs 13.6%; cOR=1.05, 95% CI 0.58 to 1.89) were comparable. CONCLUSIONS: The cumulative data of these two recent Asian trials failed to unequivocally demonstrate the non-inferiority of EVT alone over combined IVT+EVT. However, our study suggests a potential role for more individualized decision-making. Specifically, Asian patients with stroke onset to EVT longer than 180 min, as well as those with intracranial ICA occlusions and those with atrial fibrillation might have better outcomes with EVT alone than with combined IVT+EVT.

Effects of tirofiban on large vessel occlusion stroke are modified by etiology and renal function.

OBJECTIVE: Renal function can modify the outcomes of large vessel occlusion (LVO) stroke across stroke etiologies in disparate degrees. The presence of renal function deficit can also impair the pharmacokinetics of tirofiban. Hence, this study aimed to investigate the roles of renal function in determining efficacy and safety of intravenous tirofiban before endovascular treatment (EVT) for acute ischemic stroke patients with large vessel occlusion (LVO). METHODS: This study was a post hoc exploratory analysis of the RESCUE-BT trial. The primary outcome was the proportion of patients achieving functional independence (modified Rankin scale 0-2) at 90 days, and the primary safety outcome was the rate of symptomatic intracranial hemorrhage (sICH). RESULTS: Among 908 individuals with available serum creatinine, decreased estimated glomerular filtration rate (eGFR) status was noted more commonly in patients with cardioembolic stroke (CE), while large artery atherosclerosis (LAA) was predominant in patients with normal renal function. In LAA with normal renal function, tirofiban was associated with higher rates of functional independence at 90 days (41.67% vs 59.80%, p = 0.003). However, for LVO patients with renal dysfunction, tirofiban did not improve functional outcomes for any of the etiologies (LAA, p = 0.876; CE, p = 0.662; others, p = 0.894) and significantly increased the risk of sICH among non-LAA patients (p = 0.020). Mediation analysis showed tirofiban reduced thrombectomy passes (12.27%) and drug/placebo to recanalization time (14.25%) mediated its effects on functional independence. CONCLUSION: This present study demonstrated the importance of evaluating renal function before administering intravenous tirofiban among patients with LVO who are planned to undergo EVT.

Endovascular Therapy for Acute Stroke: New Evidence and Indications.

Endovascular therapy (EVT) has revolutionized the treatment of acute ischemic stroke. In the past few years, endovascular treatment indications have expanded to include patients being treated in the extended window, with large ischemic core infarction, basilar artery occlusion (BAO) thrombectomy, as demonstrated by several randomized clinical trials. Intravenous thrombolysis (IVT) bridging to mechanical thrombectomy has also been studied via several randomized clinical trials, with the overall results indicating that IVT should not be skipped in patients who are candidates for both IVT and EVT. Simplification of neuroimaging protocols in the extended window to permit non-contrast CT, CTA collaterals have also expanded access to mechanical thrombectomy, particularly in regions across the world where access to advanced imaging may not be available. Ongoing study of areas to develop include rescue stenting in patients with failed thrombectomy, medium vessel occlusion thrombectomy, and carotid tandem occlusions. In this narrative review, we summarize recent trials and key data in the treatment of patients with large ischemic core infarct, simplification of neuroimaging protocols for the treatment of patients presenting in the late window, bridging thrombolysis, and BAO EVT evidence. We also summarize areas of ongoing study including medium and distal vessel occlusion.

Association of tirofiban treatment with outcomes following endovascular therapy in cardioembolic stroke: insights from the RESCUE BT randomized trial.

BACKGROUND AND PURPOSE: The efficacy and safety of tirofiban in endovascular therapy for cardioembolic ischemic stroke patients remain controversial. This study aimed to evaluate the role of intravenous tirofiban before endovascular therapy in cardioembolic stroke. METHODS: This post hoc analysis utilized data from the RESCUE BT (Endovascular Treatment With versus Without Tirofiban for Patients with Large Vessel Occlusion Stroke) trial, which was an investigator-initiated, randomized, double-blind, placebo-controlled trial. Participants were randomized to receive either tirofiban or a placebo in a 1:1 ratio before undergoing endovascular therapy. The study included patients aged 18 years or older, presenting with occlusion of the internal carotid artery or middle cerebral artery (MCA) M1/M2 within 24 h of the last known well time, and with a stroke etiology of cardioembolism. The primary efficacy outcome was global disability at 90 days, assessed using the modified Rankin Scale (mRS). The safety outcome included symptomatic intracranial hemorrhage (sICH) within 48 h and mortality within 90 days. RESULTS: A total of 406 cardioembolic stroke patients were included in this study, with 212 assigned to the tirofiban group and 194 assigned to the placebo group. Tirofiban treatment did not correlate with a favorable shift towards a lower 90-day mRS score (adjusted common odds ratio [OR], 0.91; 95% CI 0.64-1.3; p = 0.617). However, the tirofiban group had a significantly higher risk of symptomatic intracranial hemorrhage (sICH) within 48 h (adjusted OR, 3.26; 95% CI 1.4-7.57; p = 0.006) compared to the placebo group. The adjusted odds ratio (aOR) for mortality within 90 days was 1.48 (95% CI 0.88-2.52; p = 0.143). CONCLUSIONS: Tirofiban treatment was not associated with a lower level of disability and increased the incidence of sICH after endovascular therapy in cardioembolic stroke patients.

Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials.

BACKGROUND: Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. METHODS: We conducted a systematic review and individual participant data meta-analysis to establish non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We searched PubMed and MEDLINE with the terms "stroke", "endovascular treatment", "intravenous thrombolysis", and synonyms for articles published from database inception to March 9, 2023. We included randomised controlled trials on the topic of interest, without language restrictions. Authors of the identified trials agreed to take part, and individual participant data were provided by the principal investigators of the respective trials and collated centrally by the collaborators. Our primary outcome was the 90-day modified Rankin Scale (mRS) score. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0·82 for the 95% CI around the adjusted common odds ratio (acOR) for shift towards improved outcome (analogous to 5% absolute difference in functional independence) with ordinal regression. We used mixed-effects models for all analyses. This study is registered with PROSPERO, CRD42023411986. FINDINGS: We identified 1081 studies, and six studies (n=2313; 1153 participants randomly assigned to receive endovascular treatment alone and 1160 randomly assigned to receive intravenous thrombolysis and endovascular treatment) were eligible for analysis. The risk of bias of the included studies was low to moderate. Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution. The median mRS score at 90 days was 3 (IQR 1-5) for participants who received endovascular treatment alone and 2 (1-4) for participants who received intravenous thrombolysis plus endovascular treatment (acOR 0·89, 95% CI 0·76-1·04). Any intracranial haemorrhage (0·82, 0·68-0·99) occurred less frequently with endovascular treatment alone than with intravenous thrombolysis plus endovascular treatment. Symptomatic intracranial haemorrhage and mortality rates did not differ significantly. INTERPRETATION: We did not establish non-inferiority of endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment in patients presenting directly at endovascular treatment centres. Further research could focus on cost-effectiveness analysis and on individualised decisions when patient characteristics, medication shortages, or delays are expected to offset a potential benefit of administering intravenous thrombolysis before endovascular treatment. FUNDING: Stryker and Amsterdam University Medical Centers, University of Amsterdam.

Intravenous tirofiban following successful reperfusion in intracranial large artery atherosclerotic stroke: A secondary analysis of a randomized clinical trial.

OBJECTIVE: This study aimed to investigate whether treatment with adjunct intravenous tirofiban is associated with improved outcomes following successful reperfusion in patients with intracranial atherosclerotic stroke. METHODS: Patients with intracranial large artery atherosclerotic (LAA) stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 from the Effect of Intravenous Tirofiban versus Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke (RESCUE BT) trial were included. The primary outcome was the difference in proportion of independent functional outcome (modified Rankin score of 0-2 at 90 days). Safety outcomes included the rates of symptomatic intracranial hemorrhage (sICH) and 90-day mortality. RESULTS: Among the 382 patients with intracranial LAA stroke and successful reperfusion, 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95 out of 175) with tirofiban and 44.0% (91 out of 207) with placebo (adjusted odds ratio [aOR], 1.58; 95% CI, 1.02-2.44; p = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of sICH (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59-3.34; p = 0.44) or 90-day mortality (21/175 [12.0%] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38-1.31; p = 0.27). INTERPRETATION: Among patients with acute intracranial LAA stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of sICH or mortality. Confirmatory randomized trials in these patients are desirable.

Association Between Admission Hyperglycemia and Outcomes After Endovascular Treatment in Acute Basilar Artery Occlusion.

INTRODUCTION: Admission hyperglycemia and high admission blood glucose levels have been associated with poor outcomes in acute ischemic stroke. However, the relationship between admission hyperglycemia and outcomes after endovascular treatment (EVT) in acute basilar artery occlusion (ABAO) still remain unclear. This study aimed to investigate the association between admission hyperglycemia and clinical outcomes in ABAO following EVT. METHODS: Patients from the BASILAR registry with admission blood glucose levels treated with EVT were included. We defined admission hyperglycemia as blood glucose levels ≥ 7.8 mmol/L. The primary outcome was favorable outcome [defined as a modified Rankin Scale score (mRS) of 0-3] at 90 days, Secondary outcomes included other functional outcomes (mRS 0-2, mRS 0-1) at 90 days, symptomatic intracerebral hemorrhage (sICH) within 48 h, and mortality at 90 days. RESULTS: Of 545 eligible patients included, the median age was 65 (IQR, 56-73) years, and median blood glucose level was 7.36 (IQR, 6.10-9.66) mmol/L. Multivariable logistic regression analysis showed that admission hyperglycemia was associated with decreased favorable outcome (mRS 0-3) (adjusted odds ratio = 0.52; 95% CI 0.35-0.79; P = 0.001), and increased mortality (adjusted odds ratio = 2.67; 95% CI 1.82-3.91; P < 0.001). Restricted cubic spline regression analysis showed that the blood glucose level had a non-linearity association with favorable outcome and mortality, and that there was no association between admission hyperglycemia and sICH. CONCLUSIONS: Our study suggest that admission hyperglycemia is associated with an increased risk of poor functional outcomes and mortality in patients with ABAO treated with EVT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR180001475.

Effect of collateral status on the outcomes of endovascular treatment of acute basilar artery occlusion due to large-artery atherosclerosis.

OBJECTIVE: Authors of this study aimed to evaluate the effects of collateral status on the prognostic value of endovascular treatment (EVT) in patients with basilar artery occlusion (BAO) due to large-artery atherosclerosis (LAA). METHODS: The study included 312 patients from the BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study) registry who had undergone EVT for acute BAO due to LAA and whose composite collateral scores were available. The effects of collateral status on EVT were assessed based on the composite collateral score (0-2 vs 3-5). The primary outcome was a favorable outcome (modified Rankin Scale score of 0-3) at 90 days. RESULTS: The composite collateral score was 0-2 in 130 patients and 3-5 in 182. A good collateral status (composite collateral score 3-5) was associated with a favorable outcome (66/182 [36.3%] vs 31/130 [23.8%], adjusted odds ratio [aOR] 2.21, 95% CI 1.18-4.14, p = 0.014). A lower baseline National Institutes of Health Stroke Scale (NIHSS) score was an independent predictor of a favorable outcome in the poor collateral status group (aOR 0.91, 95% CI 0.87-0.96, p = 0.001). In the good collateral status group, there was a significant correlation between favorable outcomes and a younger age (aOR 0.96, 95% CI 0.92-0.99, p = 0.016), lower baseline NIHSS score (aOR 0.89, 95% CI 0.85-0.93, p < 0.001), lower proportion of diabetes mellitus (aOR 0.31, 95% CI 0.13-0.75, p = 0.009), and shorter procedure time (aOR 0.99, 95% CI 0.98-1.00, p = 0.003). CONCLUSIONS: A good collateral status was a strong prognostic factor after EVT in patients with BAO underlying LAA. A shorter procedure time was associated with favorable outcomes in patients with a good collateral status.

Effect of Imaging Selection Paradigms on Endovascular Thrombectomy Outcomes in Patients With Acute Ischemic Stroke.

BACKGROUND: The effect of imaging selection paradigms on endovascular thrombectomy outcomes in patients with acute ischemic stroke with large vessel occlusion remains uncertain. The study aimed to assess the effect of basic imaging (noncontrast computed tomography with or without computed tomographic angiography) versus advanced imaging (magnetic resonance imaging or computed tomography perfusion) on clinical outcomes following thrombectomy in patients with stroke with large vessel occlusion in the early and extended windows using a pooled analysis of patient-level data from 2 pivotal randomized clinical trials done in China. METHODS: This post hoc analysis used data from 1182 patients included in 2 multicenter, randomized controlled trials in China that evaluated adjunct therapies to endovascular treatment for acute ischemic stroke (Direct Endovascular Treatment for Large Artery Anterior Circulation Stroke performed from May 20, 2018, through May 2, 2020, and Intravenous Tirofiban Before Endovascular Treatment in Stroke from October 10, 2018, through October 31, 2021). Patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery (M1/M2 segments) were categorized according to baseline imaging modality (basic versus advanced) as well as treatment time window (early, 0-6 hours versus extended, 6-24 hours from last known well to puncture). The primary outcome was the proportion of patients with functional independence (modified Rankin Scale score of 0-2) at 90 days. Multivariable Poisson regression analysis was performed to determine the association between imaging selection modality and outcomes after endovascular treatment at each time windows. RESULTS: A total of 1182 patients were included in this cohort analysis, with 648 in the early (471 with basic imaging versus 177 advanced imaging) and 534 in the extended (222 basic imaging versus 312 advanced imaging) time window. There were no differences in 90-day functional independence between the advanced and basic imaging groups in either time windows (early window: adjusted relative risk, 0.99 [95% CI, 0.84-1.16]; P=0.91; extended window: adjusted relative risk, 1.00 [95% CI, 0.84-1.20]; P=0.97). CONCLUSIONS: In this post hoc analysis of 2 randomized clinical trial pooled data involving patients with large vessel occlusion stroke, an association between imaging selection modality and clinical or safety outcomes for patients undergoing thrombectomy in either the early or extended windows was not detected. Our study adds to the growing body of literature on simpler imaging paradigms to assess thrombectomy eligibility across both the early and extended time windows. REGISTRATION: URL: http://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Association of Procedure Time With Clinical and Procedural Outcome in Patients With Basilar Occlusion Undergoing Embolectomy.

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated the association between the procedure time (PT) and outcomes for patients with proximal large vessel occlusion; however, whether the relationship remains for patients with acute basilar artery occlusion (ABAO) was not clear. We aimed to characterize the association between PT and other procedure-related variables on clinical outcomes among patients with ABAO who underwent endovascular treatment (EVT). METHODS: Patients with ABAO who underwent EVT with a documented PT in the EVT for Acute Basilar Artery Occlusion (BASILAR) study from January 2014 to May 2019 among 47 comprehensive centers in China were included. Multivariable analysis was performed to reveal the association between PT and 90-day modified Rankin Scale score, mortality, complications, and all-cause death at 1 year. RESULTS: Of the 829 patients from the BASILAR registry, 633 eligible patients were included. Longer PT were associated with a lower rate of favorable outcome (by 30 minutes, adjusted OR 0.82 [95% CI 0.72-0.93], p = 0.01). In addition, a PT ≤ 75 minutes was associated with a favorable outcome (adjusted OR 2.03 [95% CI 1.26-3.28]). The risk of complications and mortality increased by 0.5% and 1.5% with every 10 minutes increase in PT, respectively (R2 = 0.64 and R2 = 0.68, p < 0.01). The cumulative rates of favorable outcomes and successful recanalization plateaued after 120 minutes (2 attempts). Restricted cubic spline regression analysis for the probability of favorable outcomes had an L-shape association (p nonlinearity = 0.01) with PT with significant benefit loss before 120 minutes and then appeared relatively flat. DISCUSSION: For patients with ABAO, procedures that exceeded 75 minutes were associated with an increased risk of mortality and lower odds of a favorable outcome. A careful assessment of futility and the risks of continuing the procedure should be made after 120 minutes.

Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion.

BACKGROUND: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. METHODS: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. RESULTS: A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. CONCLUSIONS: In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).